Adco Bisocor 5mg & 10mg Tablets

ADCO BISOCOR is indicated for the management of mild to moderate hypertension and angina pectoris. It may be used alone or in combination with other antihypertensive medicines.

Posology:
Hypertension and Angina pectoris
Adults : 5 to 10 mg once a day in the morning with or without food. The dose must be individualised according to response and tolerance, in particular according to pulse rate and therapeutic success. The maximum recommended daily dose is 20 mg.

Special populations
Severe renal impairment (creatinine clearance < 30 mL/min) or severe hepatic impairment : Do not exceed the daily dose of 10 mg. There is only limited experience with the use of ADCO BISOCOR in dialysis patients. There are no indications of the necessity to alter the dose regimen.
Elderly : No dose adjustment is required in elderly patients.
Paediatric population
There is no therapeutic experience with ADCO BISOCOR in children. Its use in children is therefore not recommended (See section 4.4).

Method of administration
The film-coated tablets are to be swallowed whole in some liquid in the morning before, during or after breakfast. The duration of treatment is not limited. It depends upon the nature and severity of the disease. ADCO BISOCOR therapy should not be stopped abruptly, particularly not in patients with ischaemic heart disease, as this may lead to acute deterioration of the patientu2019s state of health (see section 4.4). If discontinuation of therapy becomes necessary, the dose should be gradually reduced (e.g. halving of the dose at weekly intervals).

• Hypersensitivity to bisoprolol or to any of the ingredients (see section 6.1).
• Uncontrolled cardiac failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy
• Cardiogenic shock
• Symptomatic hypotension
• Uncontrolled asthma or chronic obstructive pulmonary disease. Severe forms of peripheral arterial occlusive disease and Raynaudu2019s syndrome.
• Second and third degree heart (sinoarterial) block and sinus bradycardia (less than 50 beats per minute)
• Second or third degree AV block (without a pacemaker)
• Sick sinus syndrome
• Sinoatrial block
• Pregnancy (see section 4.6)
• Metabolic acidosis
• Sinus bradycardia (less than 50 beats per minute)
• Phaeochromocytoma before full alpha blockade is achieved (see section 4.4)
• Hyperthyroidism, as clinical manifestations may be masked.

Treatment with ADCO BISOCOR must not be withdrawn abruptly unless clearly indicated, since abrupt withdrawal of bisoprolol (as in ADCO BISOCOR) may lead to an acute deterioration of the patientu2019s condition in particular in patients with ischaemic heart disease (see section 4.2). Discontinuation should be gradual over a period of 1 to 2 weeks, and patients should be advised to limit the extent of their physical activity during the period in which the medicine is being discontinued.

Caution is warranted when treating patients with hypertension or angina pectoris and concomitant heart failure with ADCO BISOCOR. ADCO BISOCOR may be used only with special caution in :

• ADCO BISOCOR modifies the tachycardia associated with hypoglycaemia.
• A patient's normal tachycardic response to hypovolaemia or blood loss may be obscured during or after surgery. Particular caution should be taken in this regard and in diabetes mellitus, as symptoms and signs of hypoglycaemia may be masked, and as responses to hypoglycaemia is diminished.
• Strict fasting
• Ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine treatment may not always yield the expected therapeutic effect.
• First degree AV block
• Prinzmetalu2019s angina; Cases of coronary vasospasm have been observed. Despite its high beta1-selectivity, angina attacks cannot be completely excluded when bisoprolol is administered to patients with Prinzmetal's angina. Utmost caution must be exercised.
• Peripheral arterial occlusive disease (intensification of complaints may occur especially when starting therapy)
• ADCO BISOCOR may aggravate the symptoms of peripheral arterial occlusive disease (PAOD) or Raynaud's syndrome (due to unopposed arteriolar alpha-sympathetic activation).
• Severe peripheral vascular disease and even peripheral gangrene may be precipitated.
• Digitalisation of patients receiving long-term ADCO BISOCOR therapy may be necessary if congestive cardiac failure is likely to develop. This combination can be considered despite the potentiation of the negative chronotropic effect of the two medicines. Careful control of dosages, and of the individual patientu2019s response (and notably pulse rate), is essential in this situation.
• Particular caution should be exercised with patients suffering from the following: asthma, bronchitis, chronic respiratory diseases, peripheral vascular diseases and Raynaud's phenomenon. Tachycardia responses may be obscured. Particular caution should be taken in this regard.
• The dosage of ADCO BISOCOR should be adjusted in severe renal impairment (see section 4.2).

Combinations not recommended

• Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative effect on contractility and atrio ventricular conduction. Intravenous administration of verapamil in patients on ADCO BISOCOR treatment may lead to profound hypotension and atrioventricular block.
• Centrally acting antihypertensive medicines (e.g. clonidine, methyldopa, moxonodine) : Concomitant use of ADCO BISOCOR and centrally acting antihypertensive medicines may lead to a further reduction in heart rate and cardiac output and to vasodilation. Beta- blockers (e.g. ADCO BISOCOR) may exacerbate the u201crebound hypertensionu201d which can occur in case of abrupt withdrawal of centrally acting antihypertensive medicines (e.g. Clonidine). If the two medicines are co-administered, the u03b2 -blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by u03b2 -blocker therapy, the introduction of u03b2 -blockers should be delayed for several days after clonidine administration has stopped.

Combinations to be used with caution

• Calcium channel antagonists of the dihydropyridine type (e.g. nifedipine, amlodipine) : Concomitant use of ADCO BISOCOR and dihydropyridine calcium channel antagonists may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
• Concomitant use of ADCO BISOCOR with hypoglycaemic agents. phenothiazines and various antiarrhythmic agents can have life-threatening consequences. e.g. profound hypoglycaemia with oral hypoglycaemic agents and insulin; myocardial depression with antiarrhythmic agents.
• Class-III antidysrhythmic medicines (e.g. amiodarone) : Effect on atrio-ventricular conduction time may be potentiated.
• Class I antiarrhythmics (e.g. quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) : Effect on atrio-ventricular conduction time and negative inotropic effect may be increased.
• Parasympathomimetic medicines : Concomitant use may increase atrio-ventricular conduction time and the risk of bradycardia.
• Topical beta-blockers (e.g. eye drops for glaucoma treatment ) may add to the systemic effects of ADCO BISOCOR.
• Insulin and oral antidiabetic medicines : Increase of blood sugar lowering effect. Blockade of beta-adrenoceptors may mask symptoms of hypoglycaemia (see section 4.4).
• Anaesthesia : Attenuation of the reflex tachycardia and increase of the risk of hypotension.
• Non-steroidal anti-inflammatory drugs (NSAIDs) : NSAIDs may reduce the hypotensive effect of ADCO BISOCOR.
• Beta-sympathomimetics (e.g. dobumamine) : Combination with ADCO BISOCOR may reduce the effect of both agents. Higher doses of epinephrine (adrenaline) may be necessary for treatment of allergic reactions.
• Beta-adrenoceptor stimulating agents (e.g. isoprenaline ) may antagonise the effects of ADCO BISOCOR.
• Alpha-adrenoceptor stimulants as well as adrenergic neurone blocking agents such as guanethidine and reserpine may lead to life-threatening vasoconstriction in combination with ADCO BISOCOR.
• Sympathomimetics that activate both beta- and alpha-adrenoceptors [e.g. norepinephrine (noradrenaline), epinephrine (adrenaline)] : Combination with ADCO BISOCOR may unmask the alpha-adrenoceptor-mediated vasoconstrictor effect of these medicines leading to blood pressure increase and exacerbated intermittent claudication.
• ADCO BISOCOR and digoxin may be used concomitantly for patients with congestive heart failure provided that the pulse rate and patient response is monitored.
• Concomitant use with other antihypertensive medicines or with other medicinal products with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines ) may increase the risk of hypotension.

Combinations to be considered

• Mefloquine : Increased risk of bradycardia.
• Monoamine oxidase inhibitors (except MAO-B inhibitors) : Enhanced hypotensive effect of the beta-blockers but also risk of hypertensive crisis.
• Rifampicin : Slight reduction of the half-life of bisoprolol possible due to the induction of hepatic drug-metabolising enzymes. Normally no dosage adjustment is necessary.
• Ergotamine derivatives : Exacerbation of peripheral circulatory disturbances. In high-dose salicylate administration the toxic effect of salicylates on the central nervous system may be enhanced.

Pregnancy
ADCO BISOCOR has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. Administration of ADCO BISOCOR to pregnant mothers shortly before birth or during labour may result in hypotonia, collapse or hypoglycaemia in the newborn. (See section 4.3). ADCO BISOCOR reduces placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. bradycardia and cardiovascular collapse) may occur in the foetus and newborn infant.

Breastfeeding
It is not known whether ADCO BISOCOR is excreted in human milk. Therefore, mothers on treatment with ADCO BISOCOR should not breastfeed their infants.

Fertility
No effect on fertility was observed in male or female rats treated with bisoprolol at oral doses up to 150 mg/kg/day.

Bisoprolol, as contained in ADCO BISOCOR, may cause dizziness or fatigue and, therefore, it may adversely affect the patientu2019s ability to drive or use machinery.

Tabulated summary of adverse reactions

MedDRA System Organ Class Frequency Side effects

• Blood and the lymphatic system disorders Less frequent Blood disorders such as agranulocytosis, leukopenia and thrombocytopenia
• Unknown frequency Non-thrombocytopenic purpura, transient eosinophilia.
• Immune system disorders Less frequent Hypersensitivity (allergic) reactions (itching, flush, rash and angioedema)
• Unknown frequency Systemic Lupus Erythematosus (SLE).
• Metabolism and nutrition disorders Less frequent Increased triglycerides, raised liver enzymes (ALAT, ASAT)
• Unknown frequency Metabolic disturbances, hypoglycaemia, increase in uric acid levels, hypercholesterolaemia, hyperglycemia.
• Psychiatric disorders Less frequent Depression, sleep disorders, nightmares, hallucinations, vivid dreams and confusion, amnesia, anxiety, nervousness.
• Unknown frequency Restlessness, psychosis.
• Nervous system disorders: Frequent Dizziness*, mild headache*, drowsiness, unusual tiredness or weakness (Lassitude).
• Less frequent Syncope, paraesthesia
• Eye disorders Less frequent Dry, sore eyes, reduced tear flow (to be taken into consideration in patients wearing contact lenses), conjunctivitis.
• Unknown frequency Disturbances of vision
• Ear and labyrinth disorders Less frequent Hearing disorders.
• Unknown frequency Transient hearing loss.
• Cardiac disorders Less frequent AV-conduction disturbances, worsening of pre-existing heart failure, dysrhythmias, bradycardia, congestive cardiac failure.
• Unknown frequency Heart block
• Vascular disorders Frequent Cold extremities or numbness in the extremities, hypotension
• Less frequent Paradoxical hypertension, exacerbation of peripheral vascular disease or the development of Raynaud's phenomenon, peripheral gangrene may be precipitated and marked bradycardia may occur.
• Unknown frequency Fluid retention
• Respiratory, thoracic and mediastinal disorders Less frequent Bronchoconstriction may occur in patients suffering from asthma, bronchitis, shortness of breath or dyspnoea and other chronic pulmonary diseases. Allergic rhinitis, nasal congestion.
• Adverse reactions are more common in patients with renal decompensation.
• Unknown frequency Pneumonitis, pulmonary fibrosis, pleurisy.
• Gastrointestinal disorders: Frequent : Nausea, vomiting, diarrhoea, constipation
• Unknown frequency Mass gain, stomatitis, abdominal cramps, dry mouth.
• Hepato-biliary disorders Less frequent Hepatitis, hepatotoxicity
• Skin and subcutaneous tissue disorders Less frequent : Hypersensitivity reactions, skin rash (itching, flush, rash and angioedema), psoriasiform eruption (Beta-blockers can trigger psoriasis, aggravate the condition or lead to psoriasis form rash), reversible alopecia
• Unknown frequency Perspiration, pruritus
• Musculoskeletal, connective tissue and bone disorders Less frequent Muscle cramps, skeletal muscle weakness myopathy, back pain or joint pain, chest pain, muscle ache.
• Reproductive system and breast disorders Frequent Decreased sexual ability
• Less frequent Sexual impotence
• General disorders and administration site conditions Frequent Fatigue*,
• Less frequent Asthenia, oedema
• Unknown frequency Sclerosing peritonitis, retroperitoneal fibrosis.

*This symptom especially occurs at the beginning of therapy. It is generally mild and often disappears within 1 u2013 2 weeks.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. For reporting of side effects directly to the HCR, contact +27 11 635 0134 or email [email protected].

Symptoms
Overdosage may produce bradycardia and severe hypotension. Bronchospasm, hypoglycaemia and heart failure may be produced in certain individuals. Coma and convulsions have also been reported, and some patients may develop severe and occasionally fatal cardiovascular depression.

There is limited experience with overdose of bisoprolol, only a few cases of overdose with bisoprolol have been reported. There is a wide inter-individual variation in sensitivity to one single high dose of bisoprolol and patients with heart failure are probably very sensitive.

Treatment
The data available suggest that bisoprolol is not dialyzable to any extent. Cases of overdose should be observed for at least 4 hours, as apnoea and cardiovascular collapse may appear suddenly. Repeated activated charcoal may be necessary in overdose. Bradycardia : Atropine may be used to treat severe bradycardia. If the response is inadequate, isoprenaline or another agent with positive chronotropic properties may be given cautiously. Alternatively, dobutamine may required to reverse beta-blockade. Cardiac pacing may be required for severe bradycardia. Hypotension : Intravenous fluid replacement and administration of vasopressors. Glucagon may be given intravenously. Acute worsening of heart failure : Intravenous administration of diuretics, positive inotropic medicines, as well as vasodilators. Hypoglycaemia : Intravenous administration of glucose. Bronchospasm should be treated with IV aminophylline or inhaled or IV beta-agonist e.g. salbutamol.